Department of Anesthesiology, Attending Doctor, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University , Zhengzhou, China.
Department of Anesthesiology, Chief Physician, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University , Zhengzhou, China.
Cell Cycle. 2021 Feb;20(4):445-458. doi: 10.1080/15384101.2021.1878330. Epub 2021 Jan 28.
Both microRNAs (miRs) and dexmedetomidine (Dex) have been verified to exert functional roles in myocardial ischemia-reperfusion injury (MI/RI). Given that, we concretely aim to discuss the effects of Dex and miR-138-5p on ventricular remodeling in mice affected by MI/RI via mediating leukotriene B4 receptor 1 (Ltb4r1). MI/RI mouse model was established by ligating left anterior descending coronary artery. The cardiac function, inflammatory factors and collagen fiber contents were detected after Dex/miR-138-5p/Ltb4r1 treatment. MiR-138-5p and Ltb4r1 expression in myocardial tissues were tested by RT-qPCR and western blot assay. The target relationship between miR-138-5p and Ltb4r1 was verified by online software prediction and luciferase activity assay. MiR-138-5p was down-regulated while Ltb4r1 was up-regulated in myocardial tissues of MI/RI mice. Dex improved cardiac function, alleviated myocardial damage, reduced inflammatory factor contents, collagen fibers, and Ltb4r1 expression while increased miR-138-5p expression in myocardial tissues of mice with MI/RI. Restored miR-138-5p and depleted Ltb4r1 improved cardiac function, abated inflammatory factor contents, myocardial damage, and content of collagen fibers in MI/RI mice. MiR-138-5p directly targeted Ltb4r1. The work evidence that Dex could ameliorate ventricular remodeling of MI/RI mice by up-regulating miR-138-3p and down-regulating Ltb4r1. Thus, Dex and miR-138-3p/Ltb4r1 may serve as potential targets for the ventricular remodeling of MI/RI.
两种 microRNAs（miRs）和右美托咪定（Dex）已被证实对心肌缺血再灌注损伤（MI/RI）发挥功能作用。考虑到这一点，我们具体旨在通过调节白三烯 B4 受体 1（Ltb4r1）来讨论 Dex 和 miR-138-5p 对 MI/RI 小鼠心室重构的影响。通过结扎左前降支冠状动脉建立 MI/RI 小鼠模型。在 Dex/miR-138-5p/Ltb4r1 处理后检测心脏功能、炎症因子和胶原纤维含量。通过 RT-qPCR 和 Western blot 检测心肌组织中 miR-138-5p 和 Ltb4r1 的表达。通过在线软件预测和荧光素酶活性测定验证 miR-138-5p 和 Ltb4r1 之间的靶关系。miR-138-5p 在 MI/RI 小鼠心肌组织中下调，而 Ltb4r1 上调。Dex 改善了 MI/RI 小鼠的心脏功能，减轻了心肌损伤，降低了炎症因子含量、胶原纤维和心肌组织中 Ltb4r1 的表达，同时增加了 miR-138-5p 的表达。恢复 miR-138-5p 和耗竭 Ltb4r1 改善了 MI/RI 小鼠的心脏功能，减少了炎症因子含量、心肌损伤和胶原纤维含量。miR-138-5p 直接靶向 Ltb4r1。研究结果表明，Dex 通过上调 miR-138-3p 和下调 Ltb4r1 改善 MI/RI 小鼠的心室重构。因此，Dex 和 miR-138-3p/Ltb4r1 可能成为 MI/RI 心室重构的潜在靶点。
